Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33372 | 100339;100340;100341 | chr2:178536995;178536994;178536993 | chr2:179401722;179401721;179401720 |
| N2AB | 31731 | 95416;95417;95418 | chr2:178536995;178536994;178536993 | chr2:179401722;179401721;179401720 |
| N2A | 30804 | 92635;92636;92637 | chr2:178536995;178536994;178536993 | chr2:179401722;179401721;179401720 |
| N2B | 24307 | 73144;73145;73146 | chr2:178536995;178536994;178536993 | chr2:179401722;179401721;179401720 |
| Novex-1 | 24432 | 73519;73520;73521 | chr2:178536995;178536994;178536993 | chr2:179401722;179401721;179401720 |
| Novex-2 | 24499 | 73720;73721;73722 | chr2:178536995;178536994;178536993 | chr2:179401722;179401721;179401720 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | None | None | 0.946 | N | 0.584 | 0.274 | 0.656315445547 | gnomAD-4.0.0 | 6.84417E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9962E-07 | 0 | 0 |
| F/L | rs770089807  |
None | None | N | 0.156 | 0.254 | 0.0920862733494 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/L | rs770089807 |
None | None | N | 0.156 | 0.254 | 0.0920862733494 | gnomAD-4.0.0 | 1.36897E-06 | None | None | None | None | I | None | 5.98015E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs1691894622 |
None | 0.175 | N | 0.571 | 0.177 | 0.564872276104 | gnomAD-4.0.0 | 2.05325E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69886E-06 | 0 | 0 |
| F/Y | None | None | None | N | 0.178 | 0.151 | 0.206339911435 | gnomAD-4.0.0 | 6.84417E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9962E-07 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8692 | likely_pathogenic | 0.8081 | pathogenic | -0.667 | Destabilizing | 0.104 | N | 0.58 | neutral | None | None | None | None | I |
| F/C | 0.593 | likely_pathogenic | 0.4948 | ambiguous | -0.244 | Destabilizing | 0.946 | D | 0.584 | neutral | N | 0.437460503 | None | None | I |
| F/D | 0.9737 | likely_pathogenic | 0.9732 | pathogenic | 1.028 | Stabilizing | 0.667 | D | 0.617 | neutral | None | None | None | None | I |
| F/E | 0.9771 | likely_pathogenic | 0.9772 | pathogenic | 0.993 | Stabilizing | 0.364 | N | 0.612 | neutral | None | None | None | None | I |
| F/G | 0.9648 | likely_pathogenic | 0.9572 | pathogenic | -0.827 | Destabilizing | 0.364 | N | 0.611 | neutral | None | None | None | None | I |
| F/H | 0.7233 | likely_pathogenic | 0.7127 | pathogenic | 0.372 | Stabilizing | 0.497 | N | 0.519 | neutral | None | None | None | None | I |
| F/I | 0.6676 | likely_pathogenic | 0.5575 | ambiguous | -0.287 | Destabilizing | 0.042 | N | 0.371 | neutral | N | 0.381297789 | None | None | I |
| F/K | 0.9644 | likely_pathogenic | 0.9701 | pathogenic | 0.149 | Stabilizing | 0.22 | N | 0.6 | neutral | None | None | None | None | I |
| F/L | 0.9695 | likely_pathogenic | 0.9637 | pathogenic | -0.287 | Destabilizing | None | N | 0.156 | neutral | N | 0.452563241 | None | None | I |
| F/M | 0.8301 | likely_pathogenic | 0.8108 | pathogenic | -0.224 | Destabilizing | 0.497 | N | 0.406 | neutral | None | None | None | None | I |
| F/N | 0.8704 | likely_pathogenic | 0.8715 | pathogenic | 0.204 | Stabilizing | 0.667 | D | 0.63 | neutral | None | None | None | None | I |
| F/P | 0.9981 | likely_pathogenic | 0.9976 | pathogenic | -0.393 | Destabilizing | 0.859 | D | 0.621 | neutral | None | None | None | None | I |
| F/Q | 0.936 | likely_pathogenic | 0.9376 | pathogenic | 0.157 | Stabilizing | 0.667 | D | 0.621 | neutral | None | None | None | None | I |
| F/R | 0.9116 | likely_pathogenic | 0.9165 | pathogenic | 0.527 | Stabilizing | 0.667 | D | 0.627 | neutral | None | None | None | None | I |
| F/S | 0.7967 | likely_pathogenic | 0.7248 | pathogenic | -0.472 | Destabilizing | 0.175 | N | 0.571 | neutral | N | 0.458507778 | None | None | I |
| F/T | 0.8825 | likely_pathogenic | 0.8522 | pathogenic | -0.416 | Destabilizing | 0.364 | N | 0.558 | neutral | None | None | None | None | I |
| F/V | 0.5848 | likely_pathogenic | 0.4872 | ambiguous | -0.393 | Destabilizing | 0.042 | N | 0.507 | neutral | N | 0.401267629 | None | None | I |
| F/W | 0.5849 | likely_pathogenic | 0.5647 | pathogenic | -0.198 | Destabilizing | 0.667 | D | 0.437 | neutral | None | None | None | None | I |
| F/Y | 0.1466 | likely_benign | 0.1424 | benign | -0.119 | Destabilizing | None | N | 0.178 | neutral | N | 0.343107547 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.